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Targeted Drug Delivery to Intestinal Macrophages by Bioactive Nanovesicles Released from Grapefruit
Open accessAbstract
The gut mucosal immune system is considered to play an important role in counteracting potential adverse effects of food-derived antigens including nanovesicles. Whether nanovesicles naturally released from edible fruit work in a coordinated manner with gut immune cells to maintain the gut in a noninflammatory status is not known. Here, as proof of concept, we demonstrate that grapefruit-derived nanovesicles (GDNs) are selectively taken up by intestinal macrophages and ameliorate dextran sulfate sodium (DSS)-induced mouse colitis. These effects were mediated by upregulating the expression of heme oxygenase-1 (HO-1) and inhibiting the production of IL-1β and TNF-α in intestinal macrophages. The inherent biocompatibility and biodegradability, stability at wide ranges of pH values, and targeting of intestinal macrophages led us to further develop a novel GDN-based oral delivery system. Incorporating methotrexate (MTX), an anti-inflammatory drug, into GDNs and delivering the MTX-GDNs to mice significantly lowered the MTX toxicity when compared with free MTX, and remarkably increased its therapeutic effects in DSS-induced mouse colitis. These findings demonstrate that GDNs can serve as immune modulators in the intestine, maintain intestinal macrophage homeostasis, and can be developed for oral delivery of small molecule drugs to attenuate inflammatory responses in human disease.
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Wiklander, O. P. B., Brennan, M. Á., Lötvall, J., Breakefield, X. O., & EL Andaloussi, S. (2019) · Science Translational Medicine · doi:10.1126/scitranslmed.aav8521 · Cited by 1,039
Plant Exosome-like Nanovesicles: Emerging Therapeutics and Drug Delivery Nanoplatforms
Dad, H. A., Gu, T.-W., Zhu, A.-Q., Huang, L.-Q., & Peng, L.-H. (2021) · Molecular Therapy · doi:10.1016/j.ymthe.2020.11.030 · Cited by 745
Ginger‐derived nanoparticles protect against alcohol‐induced liver damage
Zhuang, X., Deng, Z., Mu, J., Zhang, L., Yan, J., Miller, D., Feng, W., McClain, C. J., & Zhang, H. (2015) · Journal of Extracellular Vesicles · doi:10.3402/jev.v4.28713 · Cited by 601
Self-citationRaimondo, S., Naselli, F., Fontana, S., Monteleone, F., Lo Dico, A., Saieva, L., Zito, G., Flugy, A., Manno, M., Di Bella, M. A., et al. (2015) · Oncotarget · doi:10.18632/oncotarget.4004 · Cited by 521
Plant-derived nanostructures: types and applications
Mohammadinejad, R., Karimi, S., Iravani, S., & Varma, R. S. (2016) · Green Chemistry · doi:10.1039/c5gc01403d · Cited by 437
Metadata
- Authors
- Wang, B., Zhuang, X., Deng, Z.-B., Jiang, H., Mu, J., Wang, Q., Xiang, X., Guo, H., Zhang, L., Dryden, G., Yan, J., Miller, D., & Zhang, H.-G.
- Venue
- Molecular Therapy
- Publisher
- Elsevier BV
- Published
- 2014-03
- Volume
- 22
- Issue
- 3
- Pages
- 522-534
- ISSN
- 1525-0016 (ISSN-L)
- OpenAlex
- W2134173784
- Cited by
- 634
- References
- 2
- FWCI
- 2.52
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Wang, B., Zhuang, X., Deng, Z.-B., Jiang, H., Mu, J., Wang, Q., Xiang, X., Guo, H., Zhang, L., Dryden, G., Yan, J., Miller, D., & Zhang, H.-G. (2014). Targeted Drug Delivery to Intestinal Macrophages by Bioactive Nanovesicles Released from Grapefruit. Molecular Therapy. https://doi.org/10.1038/mt.2013.190
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